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Estimated Effect of Epoetin Dosage on Survival among Elderly Hemodialysis Patients in the United States

Yi Zhang^*, Mae Thamer^*, Dennis Cotter^*, James Kaufman, and Miguel A. Hernán

^* Medical Technology and Practice Patterns Institute, Bethesda, Maryland; and Renal Section, Veterans Affairs Boston Healthcare System and Boston University School of Medicine, and Department of Epidemiology, Harvard School of Public Health, and Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts

Correspondence: Dr. Dennis J. Cotter, Medical Technology and Practice Patterns Institute, Inc., 4733 Bethesda Avenue, Suite 510, Bethesda, MD 20814. Phone: 301-652-4005; Fax: 301-652-8335; E-mail: dcott{at}mtppi.org

Background and objectives: The common finding that low achieved hemoglobin in observational studies and high target hemoglobin in randomized trials each were associated with increased mortality and high epoetin dosage has suggested the possibility that high epoetin dosage might explain the increased mortality risk.

Design, setting, participants, & measurements: We considered data from 18,454 patients who were 65 yr, were in the US Renal Data System, started hemodialysis in 2003, and survived 3 mo on dialysis. We estimated the association between cumulative average epoetin dosage and survival through the subsequent 9 mo by using inverse probability weighting to adjust for time-dependent confounding by indication.

Results: Survival was similar throughout the entire follow-up period for the three hypothetical treatment regimens selected: Low dosage 15,000 U/wk, medium dosage 30,000 U/wk, and high dosage 45,000 U/wk. Compared with a cumulative average dosage of 20,000 to 30,000 U/wk, the estimated hazard ratio (HR; 95% confidence interval [CI]) was 0.90 (0.52 to 1.54) for <10,000, 0.84 (0.67 to 1.05) for 10,000 to <20,000 U/wk, 0.96 (0.76 to 1.21) for 20,000 to <40,000 U/wk, and 0.91 (0.67 to 1.22) for >40,000 U/wk. In contrast, conventional unweighted models, which do not adequately adjust for time-dependent confounding by indication, indicated an association between high cumulative average epoetin dosage and increased mortality.

Conclusions: Our findings suggest that, on average, epoetin dosages >30,000 U/wk do not confer additional harm or benefit in elderly hemodialysis patients.

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